The effect of DNA-dependent protein kinase on adeno-associated virus replication

Young Kook ChoiDepartment of Pharmaceutics, University of Florida, Gainesville, Florida, United States of AmericaPLoS ONE 5:e15073. 2010

..DNA-dependent protein kinase (DNA-PK) is a DNA repair enzyme and plays an important role in determining the molecular fate of the rAAV genome. However, the effect this cellular enzyme on rAAV DNA replication remains elusive...

..These results demonstrated that rAAV vector-mediated BM cell-based liver gene therapy is feasible for the treatment of AAT deficiency and implies a novel therapy for the treatment of liver diseases...

..These results demonstrate the immunogenic differences of rAAV1 and rAAV8 and imply tremendous potential for these vectors in different applications, where an immune response to transgene is to be either elicited or avoided...

..Human AAT could be a potential novel therapeutic drug for the protection against neurodegeneration after ischemic stroke, but more studies are needed to investigate the protective mechanisms and efficacy in other animal models. ..

..This study indicates the potential for immunomodulatory gene therapy to prevent autoimmune diseases, including type 1 diabetes, and implicates IL-10 as a molecule capable of increasing the percentages of regulatory cells in vivo...

..These studies indicate that the risks of immune reaction and germline transmission after intramuscular injection of rAAV-SERPINA1 in nonhuman primates are relatively low within the range of vector doses studied...

Research Grants2

..Liver pathology will be examined. We anticipate achieving the therapeutic correction in PiZ transgenic mouse model. The success of this project may lead to a novel gene therapy for clinical treatment of human AAT deficiency. ..